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Melanocortin receptors and their peptide ligands

The melanocortin system consists of five G-protein-coupled receptors, peptide agonists derived from proopiomelanocortin, and the endogenous antagonists agouti and agouti-related protein. Alpha-MSH, melanotan II, PT-141 and the fragment KPV all derive from or relate to this system.

Written by the Peptency editorial teamLast reviewed 7 studies checked in PubMed on 5 October 2026

Research-use information. This page summarises published literature and regulator records. It is not guidance for use, not medical advice, and not a statement that any material is suitable for use in people or animals.

What is the melanocortin system?

A 2006 review defines the system by its five G-protein-coupled receptors, its POMC-derived peptide agonists and its endogenous antagonists, and surveys its physiological roles.[4]

What does the receptor structure show?

Cryo-EM structures of full-length human MC4R bound to alpha-MSH, afamelanotide, bremelanotide and a small-molecule ligand show how different ligands engage the same receptor. A 2022 review covers melanocortin receptor ligands beyond the melanocyte-stimulating hormones and ACTH.[3],[1]

How do the catalog compounds relate to alpha-MSH?

Melanotan II is a lactam-bridged cyclic analogue of alpha-MSH(4-10) described as a potent and unselective agonist at human melanocortin receptors. PT-141 has the same cyclic core with a C-terminal acid in place of the amide. KPV is the C-terminal tripeptide of alpha-MSH, examined in cell and mouse inflammation studies.[2],[7],[6],[5]

Which compounds in the catalog belong to this group?

Cyclic heptapeptide melanocortin receptor agonistPT-141

C50H68N14O10, 1025.2 g/mol

Cyclic heptapeptide, alpha-MSH analogueMelanotan II

C50H69N15O9, 1024.2 g/mol

Tripeptide, C-terminal fragment of alpha-MSHKPV

C16H30N4O4, 342.43 g/mol

Research materials: PT-141, Melanotan II, KPV.

Which studies are cited on this page?

  1. [1] Yuan XC, Tao YX. Ligands for Melanocortin Receptors: Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin. Biomolecules. 2022;12.

    Review of melanocortin receptor ligands beyond melanocyte-stimulating hormones and ACTH.

    ReviewPMID 36291616DOI 10.3390/biom12101407

  2. [2] Tomassi S, Dimmito MP, Cai M, D'Aniello A, Del Bene A, Messere A, et al.. CLIPSing Melanotan-II to Discover Multiple Functionally Selective hMCR Agonists. J Med Chem. 2022;65:4007-4017.

    Replaced the lactam cyclisation of melanotan II with scaffold chemistry and profiled functional selectivity at human melanocortin receptors.

    ChemistryPMID 35188390DOI 10.1021/acs.jmedchem.1c01848

  3. [3] Zhang H, Chen LN, Yang D, Mao C, Shen Q, Feng W, et al.. Structural insights into ligand recognition and activation of the melanocortin-4 receptor. Cell Res. 2021;31:1163-1175.

    Cryo-EM structures of full-length human MC4R bound to alpha-MSH, afamelanotide, bremelanotide and a small-molecule ligand.

    Structural biologyPMID 34433901DOI 10.1038/s41422-021-00552-3

  4. [4] Cone RD. Studies on the physiological functions of the melanocortin system. Endocr Rev. 2006;27:736-49.

    Review of melanocortin system physiology: receptors, POMC-derived agonists and endogenous antagonists.

    ReviewPMID 17077189DOI 10.1210/er.2006-0034

  5. [5] Luger TA, Scholzen TE, Brzoska T, Böhm M. New insights into the functions of alpha-MSH and related peptides in the immune system. Ann N Y Acad Sci. 2003;994:133-40.

    Review of alpha-MSH and related peptides in immunity and inflammation, including receptor expression on immune cells.

    ReviewPMID 12851308DOI 10.1111/j.1749-6632.2003.tb03172.x

  6. [6] Getting SJ, Schiöth HB, Perretti M. Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides. J Pharmacol Exp Ther. 2003;306:631-7.

    Compared KPV with other melanocortin peptides in a mouse model of crystal-induced peritonitis.

    Animal studyPMID 12750433DOI 10.1124/jpet.103.051623

  7. [7] Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, et al.. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58:1777-84.

    Pilot phase I study of melanotan-II in a small group of healthy volunteers (1996).

    Human studyPMID 8637402DOI 10.1016/0024-3205(96)00160-9

Data dates: citations read from PubMed 2026-10-05.